Pharmaceutical Container/Closure Integrity IV: Development of an Indirect Correlation Between Vacuum Decay Leak Measurement and Microbial Ingress

Abstract

The rational development of a physical test method to evaluate the microbial barrier properties of sterile containers necessitates its correlation to microbiological exclusion. This can be accomplished by direct or indirect correlation. In the former, the proposed physical test is directly compared to microbial challenges using appropriate test units that stimulate container leaks at both high and low probabilities of microbial ingress. Previous work has demonstrated the development of a direct correlation using helium leak rate methods and microbial immersion challenges. An indirect correlation can be established by comparing the proposed physical method to well-defined leakage standards that represent various known levels of microbial ingress. Thus the quality assurance properties of a physical test method can be established by comparison to another physical test method that has been previously characterized. This approach has the distinct advantages of being faster, quantitatively rigorous, and less subject to the vicissitudes of microbial testing. This approach was demonstrated by comparing the helium leak rate method to vacuum decay testing. Additionally it was demonstrated that vacuum decay testing was a fast and reproducible method for detecting leaks of about 1 to 2 mm. Leaks were simulated by affixing micropipettes into glass vials.